Recent advances in androgen metabolism have shown that 5 alpha-reduction of the 4 double bond in the steroid A ring and formation of 5 alpha-dihydrotestosterone is critical for androgen activation. Increased formation of 5 alpha-dihydrotestosterone has been demonstrated in certain cases of carcinoma of the breast and in the fibroadenoma of the breast implying a potential pathophysiological role for androgen metabolism in those neoplasms. The importance of androgen metabolism in carcinoma of the prostate is well documented. Because of certain histological similarities between the fibroadenoma of the breast and the uterine fibromyoma, studies were initiated incubating a fibromyoma with 3H-testosterone. Scanning of the chromatography strips demonstrated radioactivity in the 5 alpha-dihydrotestosterone, androsterone, and androstenedione areas. The extent of this testosterone metabolism appeared comparable to that shown by prostate tissue. Because of these preliminary findings, studies were initiated in our laboratory incubating samples of rat uteri with 3H-testosterone and the formation of 3H-5 alpha-dihydrotestosterone was confirmed. If androgen metabolism in the normal human uterus is comparable to that exhibited by the rat uterus, then androgen metabolism is increased in uterine neoplastic states. The object of this research proposal is to incubate tissues from normal human uteri, as well as benign and malignant uterine neoplasms with 3H-testosterone and 3H-androstenedione to study the extent of the conversion to androgenic and estrogenic metabolites.